NCT05599347

Pre-treatment With Azithromycin to Reduce Immunogenicity to to Anti-TNF Agents in Patients With Crohn's Disease

Pre-treatment With Azithromycin to Reduce Immunogenicity to Anti-Tumor Necrosis Factor-α Agents in Patients With Crohn's Disease

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: Rambam Health Care Campus · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized placebo-controlled trial in Crohn's disease patients before initiation of anti-tumor necrosis factor-α (anti-TNF) therapy that aims to test the effect of a pre-treatment short course of azithromycin therapy on immunogenicity

Detailed description

Anti-TNF agents are considered the mainstay of therapy for patients with inflammatory bowel diseases (IBD). Still, its efficacy is hampered by the development of anti-drug antibodies (ADA), which lead to non-responsiveness to this medication. A combination with immunosuppressive agents is currently utilized to reduce ADA development but is accompanied by an increased risk of side effects (i.e. malignancy and infections). The investigators have recently found an epidemiologic link between prior antibiotic use and the development of ADA, and shown an antibiotic-specific effect on ADA development in a mouse model. Macrolide antibiotics were specifically associated with ADA prevention and led to increased durability of the treatment. Since the microbiome has been associated with the response to anti-TNF therapy, the investigators hypothesize that microbial manipulation with azithromycin prior to the initiation of anti-TNF therapy will lower ADA development. the investigators propose a randomized controlled study to test our hypothesis and compare it to matched historical cohorts with available clinical and serological data. The primary outcome will be ADA development at 1 year of therapy.

Conditions

• Crohn's Disease Relapse
• Biological Substance; Adverse Effect

Interventions

Type	Name	Description
DRUG	Azithromycin Pill	Tablet - 500 mg azithromycin (as dihydrate)
OTHER	Placebo	Placebo tablet identical in shape and appearance to the azithromycin tablet used in the treatment arm

Timeline

• Start date: 2023-04-24
• Primary completion: 2025-12-31
• Completion: 2026-12-31
• First posted: 2022-10-31
• Last updated: 2025-04-04

Locations

9 sites across 1 country: Israel